Thrombin regulates tissue factor and thrombomodulin mRNA levels and activities in human saphenous vein endothelial cells by distinct mechanisms.

Bartha, K.; Brisson, Christine; Archipoff, G; Salle, Corinne de la; Lanza, François; Cazenave, J.‐P.; Beretz, Alain

doi:10.1016/s0021-9258(18)54168-5

Cited by 85 publications

(9 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Otherwise, some reports show F3 gene expression related to DNA methylation status and a possible association with adverse pregnancy outcomes such as PE and recurrent spontaneous abortions 28,46 . Additionally, F3 mRNA undergoes rapid degradation since it contains AU‐rich regions in the 3′UTR that contribute to rapid mRNA degradation 47 as well as posttranscriptional 48 and posttranslational 49 modifications that regulate protein synthesis. In this sense, our results support a role for F3 in the pathophysiology of PE; however, they must be carefully interpreted.…”

Section: Discussionmentioning

confidence: 99%

Expression of tissue factor and thrombomodulin in the placentas of pregnancies affected by early‐onset and late‐onset preeclampsia

Ayala-Ramírez

Gámez

Castro-Pontón

et al. 2021

J of Obstet and Gynaecol

View full text Add to dashboard Cite

Aim To analyze the differential genetic expression and protein localization of thrombomodulin (THBD) and tissue factor (F3) in the placentas of pregnancies affected by preeclampsia. Methods We assessed the expression of THBD and F3 by immunohistochemistry and real‐time polymerase chain reaction (PCR) in placentas from 20 PE cases: 10 early‐onset PE placentas, 10 late‐onset PE placentas, and 10 control cases (normal pregnancies). Results In cases, we found higher THBD and F3 RNA levels in placental tissue. Protein expression in controls differed from that in late‐onset PE placentas, which had lower THBD levels in syncytiotrophoblasts and amniotic cells. Likewise, late‐onset PE placentas exhibited comparatively lower F3 expression in the perivillous fibrin. In contrast, early‐onset PE had high F3 expression in the subdecidual fibrin. We found no significant differences in the F3/THBD ratio between the groups. Conclusion Our study supports evidence that shows the involvement of F3 and THBD in placental disorders. Furthermore, this finding contributes to a better understanding of the physio‐pathological role that these molecules may play in the development of this heterogeneous disease.

show abstract

Section: Discussionmentioning

confidence: 99%

Expression of tissue factor and thrombomodulin in the placentas of pregnancies affected by early‐onset and late‐onset preeclampsia

Ayala-Ramírez

Gámez

Castro-Pontón

et al. 2021

J of Obstet and Gynaecol

View full text Add to dashboard Cite

show abstract

“… 27-30 Furthermore, intracellular immune sensors such as the inflammasome promote the release of TF from pyroptotic cells, 31 leading to the dissemination of procoagulant triggers. Intravascular TF expression can be further amplified by thromboinflammatory signaling through protease-activated receptors (PARs), 32,33 complement mediators, 34-36 P-selectin–mediated leukocyte interactions, 37 and/or recognition of DAMPs. 38-40 TF neutralization prevents thrombosis during experimental bacteremia 41 and viremia, 42,43 highlighting the critical role of TF-driven coagulation in DIC.…”

Section: Pathogenesis Of Dicmentioning

confidence: 99%

Disseminated intravascular coagulation and its immune mechanisms

Popescu¹,

Lupu

2022

Blood

View full text Add to dashboard Cite

Disseminated intravascular coagulation (DIC) is a syndrome triggered by infectious and non-infectious pathologies characterized by excessive generation of thrombin within the vasculature and widespread proteolytic conversion of fibrinogen. Despite diverse clinical manifestations ranging from thrombo-occlusive damage to bleeding diathesis, DIC etiology commonly involves excessive activation of blood coagulation and overlapping dysregulation of anticoagulants and fibrinolysis. Initiation of blood coagulation follows intravascular expression of tissue factor or activation of contact pathway in response to pathogen-associated or host derived damage-associated molecular patterns. The process is further amplified through inflammatory and immuno-thrombotic mechanisms. Consumption of anticoagulants and disruption of endothelial homeostasis lower the regulatory control and disseminate microvascular thrombosis. Clinical DIC development in patients associates with worsening morbidities and increased mortality regardless of the underlying pathology, therefore timely recognition of DIC is critical to reduce the pathologic burden. Due to diversity of triggers and pathogenic mechanisms leading to DIC, diagnosis is based on algorithms that quantify hemostatic imbalance, thrombocytopenia and fibrin/ogen conversion. Since current diagnosis primarily assesses overt consumptive coagulopathies, there is a critical need for better recognition of non-overt DIC and/or pre-DIC states. Therapeutic strategies for DIC patients involve resolution of the eliciting triggers and supportive care for the hemostatic imbalance. Despite medical care, mortality in DIC patients remains high and new strategies, tailored to the underlying pathologic mechanisms, are needed.

show abstract

“…Los resultados discordantes entre mRNA y proteína se pueden deber a dos causas. Una es que ya se ha reportado anteriormente que el mRNA de FT se degrada rápidamente debido a que posee regiones ricas de AU en el extremo 3´ las cuales se han demostrado que median la degradación rápida del RNA (145). La otra causa es que sufra modificaciones postranscripcionales que regulen la síntesis de la proteína.…”

Section: Patologia Casos Controlesunclassified

“…Adicionalmente se ha descrito que la trombina aumenta los niveles de TM favoreciendo la actividad anticoagulante (145), pero se debe tener en cuenta que la TM tiene adicionalmente funciones antifibrinolíticas. La hipótesis que se plantea entonces, es que la TM se aumenta por un efecto compensatorio tratando de balancear el proceso hemostático y favoreciendo la angiogénesis y la invasión celular; pero este aumento, por otro lado disminuye la fibrinólisis activando TAFI y conlleva a una acumulación de trombos de fibrina y por consiguiente a una isquemia generando daños en la función placentaria.…”

Section: Patologia Casos Controlesunclassified

“…Adicionalmente, indican que al parecer los mecanismos involucrados son distintos. En el caso de la TM, la trombina aumenta la expresión de mRNA pero no cambia la expresión en la superficie celular, sin embargo se encontró aumento de la TM secretada al medio así como de las vesículas con TM en la superficie luminal de la célula; mientras que para FT, la trombina aumentó su expresión a nivel de mRNA así como la expresión de la proteína en la superficie de la membrana celular (145). En 1999, Zhu et al, reportaron que la actividad procoagulante de células de leucemia humana dependía de la cantidad de proteína de FT, pero principalmente de la razón de la cantidad de antígenos de FT y TM en la membrana celular (FT/TM) (153).…”

Section: Patologia Casos Controlesunclassified

See 1 more Smart Citation

Expresión de factor tisular, trombomodulina y PAI-1 en placentas de pacientes con restricción de crecimiento intrauterino o preeclampsia

Ramirez¹

View full text Add to dashboard Cite

La preeclampsia y la Restricción de crecimiento intrauterino (RCIU) son dos complicaciones de embarazo con un alto componente en la morbilidad y mortalidad perinatal. Se ha propuesto que una alteración en la hemostasis placentaria podría estar involucrada con la fisiopatología de estas entidades. El objetivo de este estudio fue evaluar la alteración en la coagulación a nivel de placenta en embarazos que cursaron con preeclampsia y RCIU. Se obtuvieron placentas de embarazos con RCIU idiopático y preeclampsia y de controles. Se realizó análisis de la expresión de RNAm por PCR en tiempo real de factor tisular, trombomodulina y PAI-1 en placenta. Adicionalmente se evaluó la expresión de hPL en el plasma de gestantes. En los resultados se encontró aumento en la expresión de factor tisular (p=0,0105), de trombomodulina (p=0,0140) en las placentas con preeclampsia, así como aumento de la razón factor tisular/trombomodulina en preeclampsia (p=0,001) y en RCIU (p=0,0411). Adicionalmente fue posible extraer y amplificar RNAm de origen fetoplacentario en el plasma de gestantes, sin embargo la diferencia entre casos y controles no fue significativa. En conclusión existe una alteración de algunos mecanismos hemostáticos locales a nivel de la placenta en embarazos que cursan con preeclampsia o RCIU.

show abstract

Thrombin regulates tissue factor and thrombomodulin mRNA levels and activities in human saphenous vein endothelial cells by distinct mechanisms.

Cited by 85 publications

References 47 publications

Expression of tissue factor and thrombomodulin in the placentas of pregnancies affected by early‐onset and late‐onset preeclampsia

Expression of tissue factor and thrombomodulin in the placentas of pregnancies affected by early‐onset and late‐onset preeclampsia

Disseminated intravascular coagulation and its immune mechanisms

Expresión de factor tisular, trombomodulina y PAI-1 en placentas de pacientes con restricción de crecimiento intrauterino o preeclampsia

Contact Info

Product

Resources

About